Thirty to forty percent of prostate cancer patients become androgen independent (resistant to anti-androgen treatment) within five years. In many instances, androgen receptor mutations in androgen-independent prostate cancer cells cause anti-androgens to act as agonists or change receptor specificity. In these cases, alternative treatment regimes are needed. Exemplary treatments can be found in U.S. Pat. No. 4,636,505, which discloses acylanilides that have anti-androgenic properties, and U.S. Pat. No. 7,057,048, which discloses 6-sulfonamido-quinolin-2-one and 6-sulfonamido-2-oxo-chromeme derivatives and their use as androgen antagonists.
Androgen receptor mutations are found in as many as 50% of metastatic, hormone refractory prostate cancer tumors. Studies suggest that 12-24% of hormone refractory tumors treated with flutamide contain the same T877A mutation.
Applicants herein disclose anti-androgens that are uniquely designed to target mutant forms of the androgen receptor that are known to impart resistance to known anti-androgens used in cancer chemotherapy. As such, these novel anti-androgens are believed to have the potential to delay the occurrence of anti-androgen resistance/anti-androgen withdrawal syndrome and to serve as a second line of defense in anti-androgen therapy when mutations to the androgen receptor give rise to anti-androgen withdrawal.